Optimization of taste-masked dapoxetine oral thin films using factorial design: in vitro and in vivo evaluation

Dapoxetine HCl is used for the treatment of premature ejaculation. Dapoxetine is primarily metabolized in the liver and kidney and its metabolites are inactive; resulting in reduced bioavailability. Also, one of the commonly encountered issues in the oral dapoxetine formulae is its bitter taste. Thus, the objective of this study was to develop and to optimize novel dapoxetine taste-masked oral thin films (OTFs), to offer a faster dissolution rate, rapid release pattern, lower liver metabolism, and better patient compliance. To achieve our goal, the applicability of either pullulan or maltodextrin as strip forming polymers were investigated in the preparation of (OTFs), while glycerol was used as a plasticizer. Also, the physicochemical characteristics of dapoxetine in a resinate complex with AmberLite(TM) -IRP69 as taste masking were evaluated. Furthermore, a 2(3) factorial design was used to study and to optimize the effect of the independent variables (strip forming polymer (X-1), glycerol (X-2) and AmberLite(TM) (X-3) amounts) on the disintegration time (Y-1), degree of elongation (Y-2), and degree of in vitro drug release in phosphate buffer pH 6.8 at 5 minutes (Q5min, Y-3) as responses. P2 batch (OTF) (pullulan 96 mg, glycerol 12 mg, AmberLite(TM) 32 mg, and dapoxetine 30 mg) was identified as an optimized formulation showing an in vitro disintegration time 9.33 s, 35.56% elongation, and 91.43% Q5min; excellent in vivo disintegration time; good overall taste acceptability and stable resinate complex.